Publications

@article{Wood2025-dw,

title = {Metabolomic characterisation of the glioblastoma invasive margin  reveals a region-specific signature},

author = {James Wood and Stuart J Smith and Marcos Castellanos-Uribe and Anbarasu Lourdusamy and Sean T May and David A Barrett and Richard G Grundy and Dong-Hyun Kim and Ruman Rahman},

doi = {10.1016/j.heliyon.2024.e41309},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-01},

journal = {Heliyon},

volume = {11},

number = {1},

pages = {e41309},

publisher = {Elsevier BV},

abstract = {Isocitrate dehydrogenase wild-type glioblastoma (GBM) is 

 characterised by a heterogeneous genetic landscape resulting 

 from dynamic competition between tumour subclones to survive 

 selective pressures. Improvements in metabolite identification 

 and metabolome coverage have led to increased interest in 

 clinically relevant applications of metabolomics. Here, we use 

 liquid chromatography-mass spectrometry and gene expression 

 microarray to profile integrated intratumour metabolic 

 heterogeneity, as a direct functional readout of adaptive 

 responses of subclones to the tumour microenvironment. 

 Multi-region surgical sampling was performed on five adult GBM 

 patients based on pre-operative brain imaging and 

 fluorescence-guided surgery. Polar and hydrophobic metabolites 

 extracted from tumour fragments were assessed, followed by 

 putative assignment of metabolite identifications based on 

 retention times and molecular mass. Class discrimination between 

 tumour regions through showed clear separation of tumour regions 

 based on polar metabolite profiles. Metabolic pathway 

 assignments revealed several significantly altered metabolites 

 between the tumour core and invasive region to be associated 

 with purine and pyrimidine metabolism. This proof-of-principle 

 study assesses intratumour heterogeneity through mass 

 spectrometry-based metabolite profiling of multi-region 

 biopsies. Bioinformatic interpretation of the GBM metabolome has 

 highlighted the invasive region to be biologically distinct 

 compared to tumour core and revealed putative drug-targetable 

 metabolic pathways associated with purine and pyrimidine 

 metabolism.},

keywords = {Glioblastoma, Invasive margin, Liquid-chromatography mass   spectrometry, Metabolomics},

pubstate = {published},

tppubtype = {article}

}